Hermona Soreq Blog: Stress Reactions: Acetylcholine

by Hermona Soreq, Professor of Molecular Neuroscience, The Hebrew University’s Edmond and Lily Safra Center for Brain Sciences

Do the Stress Reactions of Our Brain Control the Immune System -- Or Is It the Other Way Around?

In the well-known 17th-century text Le Malade Imaginaire, Molière (Jean-Baptiste Poquelin) wrote, "the mind has great influence over the body, and maladies have their origin there."

Since Molière, we now know that a diseased body and malfunctioning immune system also affect the mind.

Inflammation of the nervous system has been increasingly recognized as an important factor in multiple conditions, including Alzheimer's and Parkinson's disease. New technologies in genetic engineering and drug development are rapidly progressing to implement this knowledge for early diagnosis and creative treatment strategies that take into consideration both the brain and the body.

One area that has benefited considerably from these developments is the study of anxiety.

Historically, human stress reactions enabled our ancestors to survive attacks and protect the body from injury. But even though these reactions aren't necessities like they were for our ancestors, the same response patterns have continued to the present. An unpleasant discussion at work rarely leads to physical attacks, but our body nevertheless prepares for such attacks; it elevates the blood pressure to prepare for running, and produces more white blood cells as protection from anticipated injury.

While such reactions are useful for immediate protection -- since alertness can assist us in reacting to stressful experiences faster and more efficiently -- the consequences of stress responses may also entail long-term damages spanning muscle and nerve cells malfunctions, neurodegenerative diseases like Alzheimer's and Parkinson's, and inflammatory diseases.

The long-term and disease-provoking consequences of stress responses may take years to develop. This was not a concern for early humans, whose life span was shorter than ours (by the time stress could take its toll, they were no longer alive). But today, humans live much longer, and as a result, stress-associated diseases -- especially in the elderly -- have become a major social and financial burden.
***Over the past two decades, I, along with my colleagues at the Edmond and Lily Safra Center for Brain Sciences (ELSC) at The Hebrew University of Jerusalem, have pioneered and developed innovative strategies for investigating the consequences of traumatic experiences and designed new strategies to combat neurodegenerative diseases.

Our work has proven that in both brain neurons and blood cells, the genetic information that processes events are vulnerable to changes under stress. Moreover, we've discovered that both inherited and acquired defects in neurons, as well as traumatic experiences or exposure to a contaminated environment, contribute to delayed susceptibilities to stress-associated diseases.

The consequences may be seriously harmful, affect seemingly unrelated functions (e.g. learning and memory, the day-and-night cycle, muscle fatigue, inflammation), and last over the life spans of individuals and communities.

A good portion of our research has been devoted to a small chemical called acetylcholine, the first known neurotransmitter (a small chemical compound which is capable of activating neurons to send electrical signals) and the primary communicator between the body and the brain.

Discovered 100 years ago by the Nobel laureate Otto Loewi, acetylcholine comes from the brain through the vagus nerve and is responsible for muscle twitching. We've discovered that acetylcholine signals produced in the brain affect psychological stress responses, inflammation, aging, and the recovery from acute ischemic stroke.

As part of our research, we isolated the genes controlling acetylcholine degradation in humans and identified stress-induced changes in their expression in brain neurons and blood cells alike.

To pinpoint the physiological role of these genes, we engineered mice with excess or deficient amounts of the genes' protein products and watched their learning, muscle functioning and behavior. We learned three basic things:

1) Either too much or too rapid degradation of acetylcholine may cause cognitive deterioration, which intensifies anxiety reactions and can also intensify them, creating a vicious cycle;

2) The mice with excess breakdown of acetylcholine suffer constant inflammation, demonstrating the power of brain-to-body communication for our immune system and showing that individuals who carry inherited small changes in these genes are at increased risks for Parkinson's and Alzheimer's disease;

3) Different products of these genes may either enhance the progression of brain pathology in Alzheimer's and Parkinson's disease or help protect against them, and they also determine one's prospects to survive and recover from ischemic stroke. Measuring such changes by a simple blood test can hence predict one's prospects for recovery and the risks for post-traumatic stress disorder.

New discoveries in stress-related pathologies are occurring at a quickening pace. Just recently, we've developed a synthetic DNA-based drug for treating patients with inflammatory bowel disease.

With the help of a $5 million grant approved by the Leona M. and Harry B. Helmsley Charitable Trust, we hope that such developments will bring us closer to finding more permanent treatments for neurodegenerative and other diseases that have, unfortunately, become all too common.

Jonah Lehrer: Meta-Lessons - Fail Big, Grit, and Growing Up

For Jonah Lehrer: First we smirk, then we work.

by Don Mangus

“When I walked into the classroom of Silas Cooper, a drama teacher at the school, I couldn’t help but notice the handwritten banner hanging above the door. This is what it said: FAIL BIG.” – Jonah Lehrer, “The Shakespeare Paradox,” Imagine How Creativity Works

I greatly enjoyed Jonah Lehrer’s first two popular science books, Proust Was a Neuroscientist and How We Decide. These were written in a breezy Malcolm Gladwellesque style -- quick and fun reads, peppered with intriguing research-based observations.

I was dealt quite a surprise when I surfed over to Amazon to order his latest, Imagine How Creativity Works. Instead of finding a nicely discounted copy as expected, I found instead that the book ”was no longer available.” Frantically searching eBay and abe.com, the few copies I found listed were listed at sky-high collectible prices. How could this be? This was a brand new publication. Could the title really be that popular?

A quick fact-finding search on google revealed just the opposite. The book was now somewhat of a literary scandal – ashamedly recalled, and thus made in short supply. Apparently, according to his peers, Mr. Lehrer had taken unconscionable “journalistic shortcuts.” He “fabricated and fabulized” many of his quotes, and was also guilty of egregious blogging transgressions dubbed “self-plagarism.” Undaunted, I ordered the cheapest copy of the book I could find online. I wanted to read this book more than ever.

When it arrived, the back of the hard cover boasted two of the highest back-of-the-dust jacket accolades possible:

“Jonah Lehrer’s new book confirms what his fans have known all along – that he knows more about science than a lot of scientists and more about writing than a lot of writers.” – Malcolm Gladwell author of The Tipping Point and Outliers

“Jonah Lehrer may be the most talented explainer of science that we’ve got. His engrossing investigation of creativity and its sources makes Imagine his best book yet.” – Joshua Foer author of Moonwalking with Einstein

Ouch! After the scandal broke, such ringing endorsements might now feel a bit embarrassing to two of my all-time favorite science writers. As I read Imagine, I searched the text for clues as to what went through Jonah Lehrer’s mind -- why he took the “literary liberties” that led to his fall from grace. I think I found a few in these passages, mostly gleaned from his chapter titled “The Shakespeare Paradox” (bold emphasis mine).

(page 221) – “… But Shakespeare didn’t just read these texts and imitate their best parts: he made them his own, seamlessly blending them together in his plays. Sometimes this literary approach got Shakespeare into trouble. His peers regularly accused him of plagiarism, and he was often guilty, at least by contemporary standards. What these allegations didn’t take into account, however was that Shakespeare was pioneering a new creative method in which every conceivable source informed his art. For Shakespeare the art of creation was inseparable from the act of connection…”

(pages 246-7) -- “…But Dylan wasn’t just copying these tunes; his close study was an essential part of his creative method – learning an old song meant he was on the version of inventing a new one...

…One consequence is that virtually all of Dylan’s first seventy compositions from ’Blowin’ In the Wind’ to ‘The Times They Are a-Changin’, have clear musical precursors….

…T. S. Eliot said it best: ‘Immature poets imitate. Mature poets steal.’ Even at the age of twenty-one Dylan was a mature poet. He was already a thief.”

…What kind of culture have we created? Is it a world full of ideas that can be connected? Are we willing to invest in risk takers? Do our schools produce students ready to create?...

… We have to make it easy to become a genius.”

(pages 252-3) – “…The mystery is this: although the imagination is inspired by the everyday world – by its flaws and beauties – we are able to see beyond our sources, to imagine things that exist only in the mind. We notice an incompleteness and we can complete it; the cracks in things become a source of light…

…Every creative story is different. And every creative story is the same. There was nothing. Now there is something. It’s almost like magic.”

So it seems Jonah Lehrer took the “poetic license” and “incompleteness” parts of the creative process to heart with his “fabulized” quotes and research. He engaged in creative storytelling rather than hard-and-fast journalism or science. I for one, forgive him this sin. He certainly has FAILED BIG in the eyes of his peers.

However, I sincerely hope Mr. Lehrer will learn and recover from this “scandal” and write again. Science is always being revised anyway. I never regarded these popular science books as other than a stimulating source of wonder and inspiration.

In the grand scheme of things I prefer to save my slings and arrows for other “system gamers” such as self-serving, exempt-from-the-law Congressmen, do-nothing government watchdog agencies, and corrupt financial power brokers.

I will close my Imagine essay with some passages about persistence (or grit) and growing up from Jonah Lehrer’s book that I hope he will also take to heart.

(page 56) -- “…The reality of the creative process is that it often requires persistence, the ability to stare at a problem until it makes sense, It’s forcing oneself to pay attention, to write all night and then fix those words in the morning. It’s sticking with a poem until it’s perfect; refusing to quit on a math question…

… The answer won’t arrive suddenly, in a flash of insight. Instead, it will be revealed slowly, gradually emerging after great effort.”

(page 232-3) -- “…It doesn’t matter if people are playing jazz or writing poetry – if they want to be successful, they need to learn how to persist and persevere, how to keep working until the work is done…”

And finally,

(page 109) -- ‘’Picasso once summarized the paradox this way: ‘Every child is an artist. The problem is how to remain an artist once we grow up.”

Don’t quit, and keep writing, Mr. Jonah Lehrer. Remain an artist.